This refers to the occurrence of G-6-PD deficiency, an X-linked recessive (X-LR) disorder, in large number of females(l,2). The most important feature of X-linked inheritance is that only males are affected, while females being carrier of the gene are mostly asymptomatic. There are several mechanisms by which a female may be affected. The first is 'lyonization' or inactivation of X-chromosome. The process of inactivation is usually random, i.e., there is as much chance that the X-chromosome that carries the mutant gene will be inactivated as that the other X-chromosome will. Therefore, the female carrier usually has an even proportion (say 50%) of affected as well as normal cells, and is thus clinically disease-free. By chance, a female can have a high proportion (say 90%) of cells with nor- mal X-chromosome being inactive. In such case she will have an excessive population of cells in which the defective X-chromo- some is active and therefore, will manifest with disease. The second way a female may manifest with an X-linked recessive disease is, if she has Turner syndrome (XO geno-type) with the lone X-chromosome carrying the mutant gene. The above mentioned mechanisms however, account for occurrence of an X-LR disease in an occasional female, but fails to explain the large number of affected females in G-6-PD deficiency.

The third mechanism by which a female can manifest an X-linked disorder, is by being homozygous, i.e., both the X-chromosomes carrying the defective gene. This can happen when a carrier mother mates with

an affected father. Half of their daughters will be homozygous and affected. This mating pattern is likely to occur with those X-LR diseases which are not lethal or disabling to the male before they can enter re- productive age and produce children. G-6-PD deficiency is one such disorder, which apart from being non-lethal to the male, has a high gene frequency in the general population resulting in increased chances of an affected male (G-6-PD deficient) marrying a carrier female and producing homozygous (affected) females. In addition mating between an affected male and affected female (who are G-6-PD deficient but otherwise healthy) is also possible. All their male as well as female children then will be affected by G-6-PD deficiency. Therefore, occurrence of G-6-PD deficiency in large number of females is not an unexpected finding. Other X-linked disorders like Duchenne muscular dystrophy, Lesch-Nyhan syndrome, Menke's disease, etc. in contrast, rare very are and also severely disabling/lethal to the affected male in early life precluding any mating between them and a carrier female. That is why one does not see these X-LR disorders in large number of females.
 

Jatinder S. Goraya,
Senior Lecturer,
Department of Pediatrics,
Government Medical
College and Hospital,
Chandigarh 160047, India.
 

1. Goyal R. Glucose-6-phosphate dehydrogenase deficiency. Why girls are affected? Indian Pediatr 1998; 35: 688.

2. Jana AK. Glucose-6-phosphate dehydrogenase deficiency. Why girls are affected? Indian Pediatr 1998; 35:.688-689.